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Boundaries to movement form a specific class of landmark information used for navigation: Boundary Vector Cells (BVCs) are neurons which encode an animal's location as a vector displacement from boundaries. Here we characterise the prevalence and spatial tuning of subiculum BVCs in adult and developing male rats, and investigate the relationship between BVC spatial firing and boundary geometry. BVC directional tunings align with environment walls in squares, but are uniformly distributed in circles, demonstrating that environmental geometry alters BVC receptive fields. Inserted barriers uncover both excitatory and inhibitory components to BVC receptive fields, demonstrating that inhibitory inputs contribute to BVC field formation. During post-natal development, subiculum BVCs mature slowly, contrasting with the earlier maturation of boundary-responsive cells in upstream Entorhinal Cortex. However, Subiculum and Entorhinal BVC receptive fields are altered by boundary geometry as early as tested, suggesting this is an inherent feature of the hippocampal representation of space.

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Successfully navigating in physical or semantic space requires a neural representation of allocentric (map-based) vectors to boundaries, objects and goals. Cognitive processes such as path-planning and imagination entail the recall of vector representations, but evidence of neuron-level memory for allocentric vectors has been lacking. Here, we describe a novel neuron type, vector trace cell (VTC), whose firing generates a new vector field when a cue is encountered and a 'trace' version of that field for hours after cue removal. VTCs are concentrated in subiculum, distal to CA1. Compared to non-trace cells, VTCs fire at further distances from cues and exhibit earlier-going shifts in preferred theta phase in response to newly introduced cues, which demonstrates a theta-linked neural substrate for memory encoding. VTCs suggest a vector-based model of computing spatial relationships between an agent and multiple spatial objects, or between different objects, freed from the constraints of direct perception of those objects.

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Head direction (HD) cells are neurons found in an extended cortical and subcortical network that signal the orientation of an animal's head relative to its environment [1-3]. They are a fundamental component of the wider circuit of spatially responsive hippocampal formation neurons that make up the neural cognitive map of space [4]. During post-natal development, HD cells are the first among spatially modulated neurons in the hippocampal circuit to exhibit mature firing properties [5, 6], but before eye opening, HD cell responses in rat pups have low directional information and are directionally unstable [7, 8]. Using Bayesian decoding of HD cell ensemble activity recorded in the anterodorsal thalamic nucleus (ADN), we characterize this instability and identify its source: under-signaling of angular head velocity, which incompletely shifts the directional signal in proportion to head turns. We find evidence that geometric cues (the corners of a square environment) can be used to mitigate this under-signaling and, thereby, stabilize the directional signal even before eye opening. Crucially, even when directional firing cannot be stabilized, ensembles of unstable HD cells show short-timescale (1-10 s) temporal and spatial couplings consistent with an adult-like HD network. The HD network is widely modeled as a continuous attractor whose output is one coherent activity peak, updated during movement by angular head velocity signals and anchored by landmark cues [9-11]. Our findings present strong evidence for this model, and they demonstrate that the required network circuitry is in place and functional early during development, independent of reference to landmark information.

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New research reveals that neural activity is required for post-natal maturation of hippocampal neural circuits underlying memory and navigation; this activity-dependent maturation occurs sequentially along the classic 'tri-synaptic' pathway, following the direction of information flow found in the adult hippocampus.

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The hippocampal formation (HF) contains a neural representation of the environment, based on the activity of several classes of neurons whose firing is tuned to an animal's position and orientation in space. Recently, work has begun on understanding when and how this neural map of space emerges during development. Different classes of spatially tuned neurons emerge at different ages, some of them very early during development, before animals have started exploring their environment. The developmental timeline thus far uncovered has yielded insights into both the mechanisms of the ontogeny of the neural code for space, as well as how this system functions in the adult.

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The spatial mapping function of the hippocampal formation is likely derived from two sets of information: one based on the external environment and the other based on self-motion. Here, we further characterize 'boundary vector cells' (BVCs) in the rat subiculum, which code space relative to one type of cue in the external environment: boundaries. We find that the majority of cells with fields near the perimeter of a walled environment exhibit an additional firing field when an upright barrier is inserted into the walled environment in a manner predicted by the BVC model. We use this property of field repetition as a heuristic measure to define BVCs, and characterize their spatial and temporal properties. In further tests, we find that subicular BVCs typically treat drop edges similarly to walls, including exhibiting field repetition when additional drop-type boundaries are added to the testing environment. In other words, BVCs treat both kinds of edge as environmental boundaries, despite their dissimilar sensory properties. Finally, we also report the existence of 'boundary-off cells', a new class of boundary-coding cells. These cells fire everywhere except where a given BVC might fire.

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The role of the hippocampal formation in spatial cognition is thought to be supported by distinct classes of neurons whose firing is tuned to an organism's position and orientation in space. In this article, we review recent research focused on how and when this neural representation of space emerges during development: each class of spatially tuned neurons appears at a different age, and matures at a different rate, but all the main spatial responses tested so far are present by three weeks of age in the rat. We also summarize the development of spatial behaviour in the rat, describing how active exploration of space emerges during the third week of life, the first evidence of learning in formal tests of hippocampus-dependent spatial cognition is observed in the fourth week, whereas fully adult-like spatial cognitive abilities require another few weeks to be achieved. We argue that the development of spatially tuned neurons needs to be considered within the context of the development of spatial behaviour in order to achieve an integrated understanding of the emergence of hippocampal function and spatial cognition.

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Understanding the development of the neural circuits subserving specific cognitive functions such as navigation remains a central problem in neuroscience. Here, we characterize the development of grid cells in the medial entorhinal cortex, which, by nature of their regularly spaced firing fields, are thought to provide a distance metric to the hippocampal neural representation of space. Grid cells emerge at the time of weaning in the rat, at around 3 weeks of age. We investigated whether grid cells in young rats are functionally equivalent to those observed in the adult as soon as they appear, or if instead they follow a gradual developmental trajectory. We find that, from the very youngest ages at which reproducible grid firing is observed (postnatal day 19): grid cells display adult-like firing fields that tessellate to form a coherent map of the local environment; that this map is universal, maintaining its internal structure across different environments; and that grid cells in young rats, as in adults, also encode a representation of direction and speed. To further investigate the developmental processes leading up to the appearance of grid cells, we present data from individual medial entorhinal cortex cells recorded across more than 1 day, spanning the period before and after the grid firing pattern emerged. We find that increasing spatial stability of firing was correlated with increasing gridness.

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The mechanism supporting the role of the hippocampal formation in novelty detection remains controversial. A comparator function has been variously ascribed to CA1 or subiculum, whereas the theta rhythm has been suggested to separate neural firing into encoding and retrieval phases. We investigated theta phase of firing in principal cells in subiculum and CA1 as rats foraged in familiar and novel environments. We found that the preferred theta phase of firing in CA1, but not subiculum, was shifted to a later phase of the theta cycle during environmental novelty. Furthermore, the amount of phase shift elicited by environmental change correlated with the extent of place cell remapping in CA1. Our results support a relationship between theta phase and novelty-induced plasticity in CA1.

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Alzheimer's disease (AD) is associated with progressive memory decline. Hippocampal place cells are a well understood candidate for the neural basis of one type of memory in rodents; these cells identify the animal's location in an environment and are crucial for spatial memory and navigation. We have recorded place cells in the Tg2576 mouse model of AD, and we report that aged (16 mo) but not young (3 mo) transgenic mice show degraded neuronal representations of the environment. The level of place cell degradation correlates with the animals' (poorer) spatial memory as tested in a forced-choice spatial alternation T-maze task and with hippocampal, but not neocortical, amyloid plaque burden. Place cell recording provides a sensitive assay for measuring the amount and rate of functional deterioration in animal models of dementia as well as providing a quantifiable physiological indication of the beneficial effects of potential therapies.

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Place cells in hippocampal area CA1 are essential for spatial learning and memory. Here, we examine whether daily exposure to a previously unexplored environment can alter place cell properties. We demonstrate two previously unreported slowly developing plasticities in mouse place fields: both the spatial tuning and the trial-to-trial reproducibility of CA1 place fields improve over days. We asked whether these two components of improved spatial coding rely on the alpha-isoform of the calcium/calmodulin-dependent protein kinase II (alphaCaMKII) autophosphorylation, an effector mechanism of NMDA receptor-dependent long-term potentiation and an essential molecular process for spatial memory formation. We show that, in mice with deficient autophosphorylation of alphaCaMKII, the spatial tuning of place fields is initially similar to that of wild-type mice, but completely fails to show the experience-dependent increase over days. In contrast, place field reproducibility in the mutants, although impaired, does show the experience-dependent increase over days. Consequently, the progressive improvement in spatial coding in new hippocampal place cell maps depends on the existence of two molecularly dissociable, experience-dependent processes.

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We report the spatial and temporal properties of a class of cells termed theta-modulated place-by-direction (TPD) cells recorded from the presubicular and parasubicular cortices of the rat. The firing characteristics of TPD cells in open-field enclosures were compared with those of the following two other well characterized cell classes in the hippocampal formation: place and head-direction cells. Unlike place cells, which code only for the animal's location, or head-direction cells, which code only for the animal's directional heading, TPD cells code for both the location and the head direction of the animal. Their firing is also strongly theta modulated, firing primarily at the negative-to-positive phase of the locally recorded theta wave. TPD theta modulation is significantly stronger than that of place cells. In contrast, the firing of head-direction cells is not modulated by theta at all. In repeated exposures to the same environment, the locational and directional signals of TPD cells are stable. When recorded in different environments, TPD locational and directional fields can uncouple, with the locational field shifting unpredictably ("remapping"), whereas the directional preference remains similar across environments.

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